Mechanical imaging systems such as the scanning tunneling microscope (STM) and the atomic force microscope (AFM) have tremendous potential for imaging biological samples and biomolecules. STM and AFM have atomic resolution and are demonstrated to work in ambient atmosphere, liquid and vacuum. A major advantage of these techniques over conventional submicron imaging techniques such as SEM is that samples can be imaged in situ. This proposal focuses on developments that are requried STM can be used routinely as a laboratory tool for studying biological samples. Topics addressed are techniques for a studying nonconducting samples, techniques for studying samples immersed in conducting liquids, the effect of intense electric fields on biological sample, and instrument automation.